Utilisation du PET-FDG pour la définition des volumes cibles en radiothérapie des tumeurs de la sphère cervico-maxillo-faciale: mythe et réalité

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1 Utilisation du PET-FDG pour la définition des volumes cibles en radiothérapie des tumeurs de la sphère cervico-maxillo-faciale: mythe et réalité Vincent GREGOIRE, M.D., Ph.D. Head and Neck Oncology Program, Radiation Oncology Dept., & Center for Molecular Imaging and Experimental Radiotherapy, Université Catholique de Louvain, St-Luc University Hospital, Brussels, Belgiumrésentation

2 Few patients Various sites Sub-optimal segmentation method No validation with a ground truth No clear understanding of the issue résentation

3 Use and misuse of FDG- PET in Radiation Oncology résentation

4 Potential added-value of PET in oncology S / RxTh / CH Work-up-staging prognostic evaluation GTV/CTV Selection/delineation FDG C-methionine EF3 - F-miso - CuATSM BFU - FLT Functional Image-guided IMRT Early response evaluation Final response evaluation Early detection of recurrence résentation

5 résentation R. Wouters, 1915

6 Bayesian terminology for diagnostic imaging studies Disease status - + Test - TN + FP FN TP NPV = TN/TN+FN PPV = TP/TP+FP Test - + Disease Sensitivity = 94% Specificity = 70% Sensitivity = TP/TP+FN Specificity = TN/TN+FP Disease - + NPV = 96% PPV = 60% Test NPV = 50% PPV = 92% Sensitivity = 65% Specificity = 86% résentation

7 The use of FDG-PET for the selection of Target Volume: setting the scene Laryngeal SCC: T2-N1-M0 Q: unilateral vs bilateral neck irradiation? A: highly sensitive examination résentation

8 Detection of metastatic disease in the neck N=106 patients oral cavity tumors Neck dissection for all patients (2196 lymph nodes) Sensitivity Specificity Accuracy NPV PPV PET 70% 82% 75% 71% 81% CT 66% 69% 70% 66% 74% MRI 64% 69% 66% 62% 71% US 84% 68% 76% 79% 75% résentation Stuckensen et al., 2000

9 Detection of metastatic disease in the neck Author Site # of pts Sensitivity (%) Specificity (%) Baillet (1992) all sites Benchaou (1996) all sites Braams (1995) Oc Dammann (2005) Oc, oro Laubenbacher (1995) Oro, hypo McGuirt (1995) all sites Myers (1998) all sites Stokkel (2000) Oc, oro Stuckensen (2000) Oc Mean résentation

10 Impact of PET on the staging of patients with HNSCC Detection of metastatic disease in the neck Question: Could FDG-PET avoid unnecessary treatment of the neck in 2/3 of the cn0 patients? Is FDG-PET accurate enough to modify the standard neck treatment policy? Answer: FDG-PET does not prevent neck treatment in N0 patients bearing high risk of occult metastasis FDG-PET is not more accurate than CT or MRI to allow modification of the standard neck treatment policy résentation

11 Detection of N2-N3 in NSCLC Poncelet Pieterman Kernstine n CT PET CT PET PET sens spec PPV NPV Acc Poncelet et al. Eur J Cardiothorac Surg 2001;20: Pieterman et al. N Engl J Med 2000;343: Kernstine et al. Ann Thorac Surg 2002;73: résentation

12 Potential added-value of PET in oncology résentation Antoch et al., 2004

13 Target résentation J. John, 1974

14 H&N IMRT practice heterogeneity é r P n e s n it o ta M A R P A EN Harari et al., 2005

15 Target selection and delineation Betrayal of images This is not an apple R. Magritte résentation

16 Image-Guided Radiation Therapy in HNSCC The Gross Target Volume (GTV) is the gross demonstrable extend and location of the malignant growth? résentation ICRU report 50, 1993

17 The Gross Tumor volume (GTV) résentation Daisne et al., Radiology, 233: , 2004

18 How far are we from the truth? Before treatment start Image acquisition patient fixed in a thermoplastic mask CT MRI FDG-PET Met-PET Axial sections 2.0 mm thick Contrast medium Axial sections Body coil T1, T1 + gado, T2 3D acquisition Attenuation Correction Filtered Backprojection résentation

19 5 cm Macroscopy 5 cm CAT Scan 5 cm 18 F-FDG PET résentation Daisne et al, 2003

20 What tools do we need to make our dream come to reality? Volume delineation based on automatic thresholding with 18 F-FDG OSEM (unsmoothed) OSEM (smoothed at 6 mm) 1.1 cm cm 3 résentation

21 How far are we from reality? Validation with a gold standard Vol. (ml) Mismatch x/ct Mismatch x/mr Mismatch x/pet Mismatch x/macro CT % 48% 81%? MR % - 67% 107% FDG-PET 16.3* 17% 15% - 47% Macroscopy 12.6* 10% 9% 13% - *p<0.05 (Wilcoxon rank test) résentation Daisne et al, 2003

22 Clinical Target Volume (CTV) for oropharyngeal SCC 2 1 Body of C résentation

23 Image-Guided Radiation Therapy in HNSCC Impact of imaging modality on CTV/PTV delineation Larynx/hypopharynx (n=9) Oropharynx (n=10) Average (± sem) volume (cc) CT-scan FDG-PET ANOVA: p<0.05 GTV CTV PTV Average (± sem) volume (cc) CT-scan FDG-PET ANOVA: p<0.01 GTV CTV PTV Geets et al, 2003 résentation

24 Image-Guided Radiation Therapy in HNSCC Impact of imaging modality on dose distribution CT-based target volume FDG PET-based target volume résentation

25 4D-IMRT The Cathedral of Rouen é r P n e s n it o ta M A R P A EN C. Monet, 1894

26 CT MRI (T2) FDG-PET PRE-R/ (Week 2) WEEK 3 (Week 4) WEEK 5 résentation

27 Image-Guided Radiation Therapy in HNSCC The 4th dimension FDG-PET 0 Gy 46 Gy Mucositis Tumor Geets et al, 2003 résentation

28 PET image segmentation during RxTh UG 4mm SBR Raw image W&C Image processing BG 6mm + deconvolution Image segmentation résentation

Target Volume modification during RT % of the initial volume % of the initial volume 100% 80% 60% 40% 20% 100% 80% 60% 40% 20% CT-scan relative CT-based volumes 0% 0 10 20 30 40 50 delivered dose

29 Target Volume modification during RT % of the initial volume % of the initial volume 100% 80% 60% 40% 20% 100% 80% 60% 40% 20% CT-scan relative CT-based volumes 0% delivered dose (Gy) T2 FS MRI relative FS T2-MRI-based volumes 0% delivered dose (Gy) ANOVA p < % of the initial volume % of the initial volume 100% 100% 80% 60% 40% 20% 80% 60% 40% 20% T2 MRI relative T2-MRI-based volumes 0% delivered dose (Gy) FDG-PET relative PET-based volumes (static) 0% delivered dose (Gy) Pre-R/ Week 2 Week 3 Week 4 Week 5 résentation Geets, 2006

30 Work in progress Time 1 (t 1 ) Deformed checkerboard showing the non- rigid transformation from t 1 to t 2 Deformed contour Deformed dose at t 1 on CT at t 2 Time 2 (t 2 ) résentation

31 Image-Guided Radiation Therapy in HNSCC What could we dream of Hypoxia: 18 F-EF3 Proliferation: 76 Br-BFU Metabolism: 18 F-FDG 11 C-Met résentation

32 Tumor Hypoxia [ 18 F] EF3 [ 18 F]-EF3 tracer Hypopharyngeal SCC 2,6 tumor-to-body ratios Tumor-to-background ratio 2,4 2,2 ratio 2 1,8 1,6 1,4 1, time after injection (h) tumor node résentation P Mahy, 2005

Image-Guided Radiation Therapy in HNSCC Conclusions Change in TV selection depends on the sensitivity and the specificity of FDG-PET compared to conventional methods.

33 Image-Guided Radiation Therapy in HNSCC Conclusions Change in TV selection depends on the sensitivity and the specificity of FDG-PET compared to conventional methods. Change in TV selection is thus highly tumor-site dependent. Providing that a strict methodology is used, FDG-PET GTV might be closer to the ground truth for HNSCC. Use of FDG-PET during RxTh needs further validation. Biological IGRT based on new PET tracers should remain in the research arena. résentation

34 The debate is not anymore "to PET or not to PET", but "when is it adequate to PET"! R. Wouters, 1914 résentation

This house believes that the use of Functional Imaging for treatment planning of head and neck tumors needs to be carefully considered.

This house believes that the use of Functional Imaging for treatment planning of head and neck tumors needs to be carefully considered. IMRT for Head and Neck Tumors Vincent GREGOIRE, M.D., Ph.D., Hon.